Significance of Microbiota in Obesity and Metabolic Diseases and the Modulatory Potential by Medicinal Plant and Food Ingredients. Hoda M. Eid, Natural Health Products and Metabolic Diseases Laboratory Michelle L. Wright, Emory University N.V Anil Kumar, Manipal University Abdel Qawasmeh, Hebron University Sherif T. S. Hassan, University of Veterinary and Pharmaceutical Sciences Brno Andrei Mocan, Iuliu Hatieganu University of Medicine and Pharmacy Seyed M. Nabavi, Baqiyatallah University of Medical Sciences Luca Rastrelli, University of Salerno Atanas G. Atanasov, Institute of Genetics and Animal Breeding Pierre S. Haddad, Natural Health Products and Metabolic Diseases Laboratory Journal Title: Frontiers in Pharmacology Volume: Volume 8 Publisher: Frontiers Media | 2017, Pages 387-387 Type of Work: Article | Final Publisher PDF Publisher DOI: 10.3389/fphar.2017.00387 Permanent URL: https://pid.emory.edu/ark:/25593/s4366 Final published version: http://dx.doi.org/10.3389/fphar.2017.00387 Copyright information: © 2017 Eid, Wright, Anil Kumar, Qawasmeh, Hassan, Mocan, Nabavi, Rastrelli, Atanasov and Haddad. This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). Accessed September 24, 2021 4:14 PM EDT REVIEW published: 30 June 2017 doi: 10.3389/fphar.2017.00387 Significance of Microbiota in Obesity and Metabolic Diseases and the Modulatory Potential by Medicinal Plant and Food Ingredients Hoda M. Eid 1, 2, 3, Michelle L. Wright 4, N. V. Anil Kumar 5, Abdel Qawasmeh 6, Sherif T. S. Hassan 7, Andrei Mocan 8, 9, Seyed M. Nabavi 10, Luca Rastrelli 11, Atanas G. Atanasov 12, 13, 14* and Pierre S. Haddad 1, 2* 1 Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology and Physiology, Université de Montréal, Montréal, QC, Canada, 2 Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines, Montréal, QC, Canada, 3 Department of Pharmacognosy, University of Beni-Suef, Beni-Suef, Egypt, 4 Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, United States, 5 Department of Chemistry, Manipal Institute of Technology, Manipal University, Manipal, India, 6 Faculty of Pharmacy, Hebron University, Hebron, Palestine, 7 Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czechia, 8 Department of Pharmaceutical Botany, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, 9 ICHAT and Institute Edited by: for Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania, 10 Applied Kalin Yanbo Zhang, Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran, 11 Dipartimento di Farmacia, University of Hong Kong, Hong Kong University of Salerno, Fisciano, Italy, 12 Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, 13 14 Reviewed by: Poland, Department of Pharmacognosy, University of Vienna, Vienna, Austria, Department of Vascular Biology and Adeyemi Oladapo Aremu, Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria University of KwaZulu-Natal, South Africa Metabolic syndrome is a cluster of three or more metabolic disorders including insulin Jelena Cvejic, University of Novi Sad, Serbia resistance, obesity, and hyperlipidemia. Obesity has become the epidemic of the *Correspondence: twenty-first century with more than 1.6 billion overweight adults. Due to the strong Atanas G. Atanasov connection between obesity and type 2 diabetes, obesity has received wide attention [email protected] Pierre S. Haddad with subsequent coining of the term “diabesity.” Recent studies have identified unique [email protected] contributions of the immensely diverse gut microbiota in the pathogenesis of obesity and diabetes. Several mechanisms have been proposed including altered glucose and Specialty section: This article was submitted to fatty acid metabolism, hepatic fatty acid storage, and modulation of glucagon-like Ethnopharmacology, peptide (GLP)-1. Importantly, the relationship between unhealthy diet and a modified gut a section of the journal microbiota composition observed in diabetic or obese subjects has been recognized. Frontiers in Pharmacology Similarly, the role of diet rich in polyphenols and plant polysaccharides in modulating gut Received: 28 February 2017 Accepted: 02 June 2017 bacteria and its impact on diabetes and obesity have been the subject of investigation Published: 30 June 2017 by several research groups. Gut microbiota are also responsible for the extensive Citation: metabolism of polyphenols thus modulating their biological activities. The aim of this Eid HM, Wright ML, Anil Kumar NV, Qawasmeh A, Hassan STS, Mocan A, review is to shed light on the composition of gut microbes, their health importance and Nabavi SM, Rastrelli L, Atanasov AG how they can contribute to diseases as well as their modulation by polyphenols and and Haddad PS (2017) Significance of polysaccharides to control obesity and diabetes. In addition, the role of microbiota in Microbiota in Obesity and Metabolic Diseases and the Modulatory Potential improving the oral bioavailability of polyphenols and hence in shaping their antidiabetic by Medicinal Plant and Food and antiobesity activities will be discussed. Ingredients. Front. Pharmacol. 8:387. doi: 10.3389/fphar.2017.00387 Keywords: microbiota, natural products, food ingredients, obesity, metabolic diseases Frontiers in Pharmacology | www.frontiersin.org 1 June 2017 | Volume 8 | Article 387 Eid et al. Microbiota, Medicinal Plants, and Food Ingredients DEFINITION OF HUMAN MICROBIOTA Major Bacteria Colonizing Healthy Human Gut The human microbiota (microflora) refers to an aggregation of Earlier studies aiming to reveal the identity of microbiota in the a mixture of microorganisms (e.g., bacteria, fungi, archaea, and gut of healthy humans have relied on culturing the microbes viruses) that live in human tissues such as skin, uterus, lungs, from fecal samples. Bacteria constitute most of the microbes and in the gastrointestinal tract without causing pathological colonizing human gut with species belonging to Firmicutes and responses in the host (Hugon et al., 2016). Instead these Proteobacteria phyla being predominant (Eggerth and Gagnon, organisms form a symbiotic relationship with their host. In this 1933; Zubrzycki and Spaulding, 1962). To a lesser extent, species relationship, the host provides a shelter and nutrition for the belonging to other phyla such as Actinobacteria, Bacteroidetes, microbes, while the microbes provide the host with essential and Fusobacteria are also present (Eggerth and Gagnon, 1933; metabolites such as vitamin K, thiamine, biotin, folic acid, and Zubrzycki and Spaulding, 1962). In later studies, several bacterial vitamin B12, digesting polysaccharides into simpler molecules, species, mostly anaerobic, have been identified in fecal samples boosting the immunity to combat pathogens, and competing obtained from 20 healthy individuals using improved cultural with the latter for survival (Santacruz et al., 2010; D’Aimmo techniques (Moore and Holdeman, 1974; Holdeman et al., 1976). et al., 2012; LeBlanc et al., 2013). Beyond their traditional benefits, At least 400 bacterial species were suggested to colonize human recent studies have implicated microbes residing human gut gut and a total of 113 species have been fully recognized in in modulating brain development (Wang and Wang, 2016), the tested samples (Moore and Holdeman, 1974; Holdeman altering metabolic functions (Martinez et al., 2016), hormones et al., 1976); major microbes identified being summarized in and neurochemical production (Baothman et al., 2016). Some Tables 1– 5. 30 years ago, human gut microbiota was largely ignored as a Until recently, culture-based studies aimed to identify causative factor for illnesses and as a target for pharmacological bacterial species in human gut were considered to be limited in intervention. Scientists were focused mainly on finding a novel their ability to fully evaluate bacterial diversity in human gut. pathogenic bacteria residing in the gut as an underlying cause This was based on the fact that such techniques cannot recover all of illnesses and as a target for drug development (Eggerth and species residing in the human gut (Gerritsen et al., 2011). Lau and Gagnon, 1933; Dalton, 1951; Walther and Millwood, 1951). In colleagues showed that culture-enriched techniques associated recent years, there has been an increasing trend in this area with molecular profiling are alternative effective techniques to of research, and the focus has been shifted toward identifying study microbial diversity in human gut (Lau et al., 2016). microbial composition of the human gut microbiota (Figure 1), Fecal samples from two healthy donors have been cultured the factors altering this composition, and relating it to the aerobically and anaerobically in 33 different culture media pathogenesis of some diseases such as diabetes (Yamaguchi et al., creating 66 different culture conditions. Cultured samples were 2016), autism (Berding and Donovan, 2016), obesity (Valsecchi then analyzed using 16S rRNA gene sequencing. In the previous et al., 2016), and other disorders (Gondalia et al., 2012; Baothman study (Lau et al., 2016), 95% of the bacteria residing human et al., 2016). In this review, we discuss the